A Phase 1/2 interventional study of vismodegib and Temozolomide in Histologically Confirmed Medulloblastoma and Activation of the Sonic Hedgehog (SHH) Pathway, sponsored by Centre Leon Berard. Terminated at 15 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-21.
Sponsored by Centre Leon Berard · Phase 1/2, Interventional, and Treatment
The purpose of this study is to evaluate the safety of vismodegib in combination with temozolomide (primary objective - phase I) and to estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory medulloblastomas to standard therapy measured by the 6-month progression-free rate (phase II).
This study is an open-label Phase I/II, international, randomized.
38 patients will be included in the study.
Secondary objectives are :
phase I : to collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide
PHASE II
To estimate in the two study arms:
238 studies on the registry are indexed under Medulloblastoma; 51 are open to participants now.
This study's enrollment of 24 is below the median of 35 across 198 interventional studies indexed under Medulloblastoma.
Browse Medulloblastoma studies →Centre Leon Berard is the lead sponsor of 206 studies on the registry; 61 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Neutrophils ≥ 1. 5 G/L Platelets ≥ 100 G /L Hemoglobin ≥ 10g/dL Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula or MDRD formula for patients older than 65 years ) or serum creatinine within normal limits or less than 1.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 ULN ALAT and ASAT ≤ 2.5 ULN Serum albumin ≥ 25 g/L.
No prior hedgehog antagonist vismodegib or other antagonists of the hedgehog pathway, and no prior temozolomide treatment for patients to be randomized in Arm A or B. Patients previously treated with temozolomide are eligible for enrollment in study arm C on a case by case basis and following sponsor agreement More than 4 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas, 6 months after high dose therapy) or immunotherapy At least 3 months since prior craniospinal irradiation (≥ 23 Gy) At least 8 weeks since prior local irradiation to primary tumor At least 2 weeks since prior focal irradiation for symptomatic metastatic sites.
At least 1 week since prior colony-stimulating factors (e.g., G-CSF, GM-CSF, or erythropoietin)
Women of childbearing potential* are required to have a negative serum pregnancy test within 72 hours prior to study treatment initiation (i.e. Cycle 1 Day 1).
*: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
≥50 years old and naturally amenorrheic for ≥ 1 year Permanent premature ovarian failure confirmed by a specialist gynaecologist Previous bilateral salpingo-oophorectomy XY genotype, Turner's syndrome, or uterine agenesis Female patient who do not meet at least of the above criteria are defined as women of childbearing potential.
Exclusion Criteria:
In the first step of the study (Phase I), 9 adult patients with relapsing or refractory medulloblastoma will be randomized (randomization ratio 2:1) to receive - Arm A: the combination of vismodegib (150 mg/day continuously) with temozolomide (150 mg/m2 during Cycle 1 \[day 1 to day 5/ 28 day-cycle\] and 200 mg/m2 during subsequent cycles) (6 patients)
Drug: vismodegib · Drug: Temozolomide
In the first step of the study (Phase I), 9 adult patients with relapsing or refractory medulloblastoma will be randomized (randomization ratio 2:1) to receive Arm B: temozolomide alone (150 mg/m2 day1 to day 5/ 28 day-cycle during Cycle 1 and 200 mg/m2 day 1 to day 5/ 28 day-cycle during subsequent cycles) (3 patients).
Drug: Temozolomide
Considering the rarity of the disease, the few therapeutic options available and the promising results reported with vismodegib in adult medulloblastoma : the Sponsor will consider (on case by case basis) the enrolment of patients previously treated by temozolomide in a 3rd independent and parallel study arm
Drug: vismodegib
Hedgehog pathway antagonist Dosage: 150 mg orally with or without food at the same time every day
alkylating agent Dosage: Dose in Cycle 1 is 150 mg/m2 orally once daily for 5 days followed by 23 days without treatment. At the start of Cycle 2, the dose is escalated to 200mg/m2 orally once daily for 5 days
Also known as: temodal
To evaluate the safety of a fixed dose of vismodegib in combination with (phase I)temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma
number of severe toxicities occurring during the first 3 months of follow-up : * Toxic death * Grade 4 toxicity * Any grade 3 AE leading to study treatment interruption for more than 7 days or discontinuation.
Time frame: during the first three months follow up
To estimate the efficacy of vismodegib in combination with temozolomide in adult patients with recurrent, progressive, or refractory to standard therapy medulloblastoma (phase II)
the 6-month progression-free rate
Time frame: 6 months after start of treatment
To collect preliminary results on the 6-month progression-free rate of the combination vismodegib + temozolomide (phase I)
measurement of progression free rate
Time frame: 6 months after start of treatment
To estimate in the two study arms the objective response rate after 6 months of treatment (phase II)
measure by objective response rate
Time frame: after 6 months of treatment
To estimate in the two study arms the duration of treatment response (phase II)
treatment response
Time frame: one year
To estimate in the two study arms the best overall response obtained during the study (phase II)
Time frame: one year
To estimate in the two study arms the progression-free survival (PFS)(phase II)
measure of progression free rate
Time frame: one year
To estimate in the two study arms the time to treatment failure (phase II)
Time frame: one year
frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade
In the combination arm (vismodegib + temozolomide): to further evaluate the safety of the combination
Time frame: one year
This study is terminated, as verified in May 2019. You cannot join it, but the record below documents what was studied.
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